The fatty acid content of neural tissues in the brain changes throughout development, with progressive enrichment of phospholipids with long chain polyunsaturated fatty acids (LCPs), especially during the last pre-natal trimester and the first 6 months post-natal. Under optimal conditions, LCPs are supplied to the fetus via placental transfer and to the infant via breast-feeding post-natally. However, only 60% of U.S. newborns are breast-fed and 60-80% of breast-fed infants are weaned by 12 weeks of age. Formula feeding deprives infants of pre-formed LCPs since they are not provided in U.S. infant formulas. The last trimester of pre-natal development and the first year of life are periods of rapid increase in the number of synapses and dendritic arborizations in the brain. Since these processes require the deposition of LCPs in neuronal membranes, any limitation of LCP supply may modify the growth and function of the central nervous system. While the focus of research on LCP supplementation of infant formula has been on the first 2-4 months of life, little is known about the critical period during which dietary LCPs influence the maturation of cortical function. In Aim 1, we will conduct a randomized trial of LCP supplementation of term infants during months 4-12. We will delineate the critical period for cortical LCP accretion by comparing neurodevelopmental outcomes from this cohort with our existing term infant data sets from randomized trials of LCP supplementation during the first weeks or months of life. The argument that LCPs are present in human milk as a basis for their inclusion in infant formula is compelling but limited by the lack of data on the short-term and long-term effects of dietary LCP supplements in formula-fed infants. In Aim 2, metabolic and nutritional effects of LCPs will be evaluated in terms of alterations in hemostasis, antioxidant defense mechanisms, and lipid profiles. These functional and biochemical parameters are considered of particular importance to assessing the short-term and long-term safety of LCP-supplementation to the nation's infant formula supply. Visual evoked potential and preferential looking acuity have been used widely as outcome measures in studies of infant LCP nutrition, with the inference that these visual outcomes are related to other aspects of cortical function; i.e., cognitive function. In Aim 3, we propose to obtain the first long-term cognitive outcome data for large samples of infants who participated in randomized trials of LCP-supplemented formula. By relating long-term outcomes to visual cortical function during infancy, we will directly evaluate the predictive of early visual tests for long-term cognitive outcomes.